204 P. Y. J. Yeh, J. N. Kizhakkedathu and M. Chiao
had improved the patients’ life quality. However, with the advances of these
technologies, the view of biocompatibility had extended from the “the host tol-
erates the device” to “the device tolerates the host and vice versa”.
a subcutaneous glucose sensor comprises of immobilized enzymes, electrodes and
a semi-permeable membrane. The semi-permeable membrane acts as a protecting
layer that keeps the enzyme and electrodes from the attack of the immune system
and it allows glucose from interstitial space to diffuse through. In order to be
successful, the semi-permeable membrane must not induce pathogenic reactions
to the host. On the other hand, the glucose permeability of the membrane must be
maintained at all times. Hence, the problem of biofouling needs to be reduced as
much as possible.
Biofouling is a process started immediately after a foreign object comes into
contact with biological ﬂuids because of the immune response system. And it is
considered to be one of the greatest challenges of medical implantation.
immediate response is to ﬂood the injured area with blood followed by adsorption
of blood proteins onto the implant surface and activation of the molecular and
cellular defense systems.
The coagulation, complement, immune and inﬂamma-
tory pathways can all be initiated by this process as can platelet and white cell
activation. The extent to which these responses occur depends on the nature of
the protein adsorption, speciﬁc binding or rejection reactions that occur at the
impalnt-blood interface. Usually an adsorbed protein layer of thickness from
0.5 to 9 μm accumulates over time. Approximately 21 days after implantation,
an avascular ﬁbrous capsule of up to 100 μm will form around the implant and
may reduce its performance.
Prevention of protein adsorption unto implants
is critical for increasing their longevity. Some methods had been provided so
far, such as polymer-based coatings,
plasma surface functionalization,
and ﬂow ﬂushing upon the
etc. Coatings, surface roughness, surface topography are catalogued
as passive methods, while physical means, such as mechanical vibration and ﬂow
ﬂushing are considered as active methods of anti-biofouling.
Numerous studies have indicated that the surface chemistry of and
microstructure on the implant surface can modulate protein adsorption.
among those passive methods, polymer coating is attractive for certain applica-
tions, such as long-circulating sterically protected liposome,
Those polymer candidates usually are composed by three parts,
anchor to surface, monomer repeated backbone, and end functional group.
The most popular polymer used is probably the hydrophilic poly(ethylene gly-
col) (PEG). When there is sufﬁcient high PEG graft density, the coiled PEG with one
end anchored to the surface will form brushes by extending the coils away from
surface, and so that to create a steric barrier from protein adsorption.
polymer coatings are successful for short term and often fail in the case of a
highly complex mixture of proteins, for example, blood plasma,
or under in vivo
As an alternative to polymer coating, researchers have also fabricated
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